EP3272870A1 - Compositions permettant d'inhiber l'expression de gènes et leurs utilisations - Google Patents
Compositions permettant d'inhiber l'expression de gènes et leurs utilisations Download PDFInfo
- Publication number
- EP3272870A1 EP3272870A1 EP17190602.7A EP17190602A EP3272870A1 EP 3272870 A1 EP3272870 A1 EP 3272870A1 EP 17190602 A EP17190602 A EP 17190602A EP 3272870 A1 EP3272870 A1 EP 3272870A1
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- EP
- European Patent Office
- Prior art keywords
- seq
- oligonucleotide
- oligonucleotides
- dna
- based compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/15—Nucleic acids forming more than 2 strands, e.g. TFOs
- C12N2310/152—Nucleic acids forming more than 2 strands, e.g. TFOs on a single-stranded target, e.g. fold-back TFOs
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3519—Fusion with another nucleic acid
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/51—Physical structure in polymeric form, e.g. multimers, concatemers
Definitions
- accessible generally means when related to a compound according to the invention, that the relevant portion of the molecule is able to be recognized by the cellular components necessary to elicit an intended response to the compound.
- co-administration or “co-administered” generally refers to the administration of at least two different substances sufficiently close in time to modulate an immune response. Co-administration refers to simultaneous administration, as well as temporally spaced order of up to several days apart, of at least two different substances in any order, either in a single dose or separate doses.
- kinase inhibitor generally refers to molecules that antagonize or inhibit phosphorylation-dependent cell signaling and/or growth pathways in a cell.
- Kinase inhibitors may be naturally occurring or synthetic and include small molecules that have the potential to be administered as oral therapeutics.
- Kinase inhibitors have the ability to rapidly and specifically inhibit the activation of the target kinase molecules.
- Protein kinases are attractive drug targets, in part because they regulate a wide variety of signaling and growth pathways and include many different proteins. As such, they have great potential in the treatment of diseases involving kinase signaling, including cancer, cardiovascular disease, inflammatory disorders, diabetes, macular degeneration and neurological disorders.
- a non-limiting example of a kinase inhibitor is sorafenib.
- nucleic acid encompasses a genomic region or an RNA molecule transcribed therefrom. In some embodiments, the nucleic acid is mRNA.
- each nucleoside unit includes a heterocyclic base and a pentofuranosyl, trehalose, arabinose, 2'-deoxy-2'-substituted nucleoside, 2'-deoxy-2'-substituted arabinose, 2'-O-substitutedarabinose or hexose sugar group.
- the nucleoside residues can be coupled to each other by any of the numerous known internucleoside linkages.
- physiologically acceptable refers to a non-toxic material that is compatible with a biological system such as a cell, cell culture, tissue, or organism.
- a biological system such as a cell, cell culture, tissue, or organism.
- the biological system is a living organism, such as a mammal, particularly a human.
- an antisense oligonucleotide according to the invention requires many considerations beyond simple design of a molecule that is complementary to the target RNA sequence.
- preparation of antisense oligonucleotides according to the invention is intended to incorporate changes necessary to limit secondary structure interference with antisense activity, enhance the oligonucleotide's target specificity, minimize interaction with binding or competing factors (for example, proteins), optimize cellular uptake, bioavailability, pharmacokinetics, and pharmacodynamics, and/or inhibit, prevent or suppress immune cell activation.
- L is a nucleotide linker or non-nucleotide linker; N1-N8, at each occurrence, is independently a nucleotide or nucleotide derivative; Nm and Nn, at each occurrence, are independently a nucleotide or nucleotide derivative; and wherein m and n are independently numbers from 0 to about 40.
- Representative non-nucleotide linkers are set forth in Table 1.
- L is a linker or a nucleotide linkage and Domain A and/or Domain B are antisense oligonucleotides that are designed to selectively hybridize to the same target RNA sequence or different target RNA sequences.
- re-administration to a donor or administration to a second patient having cancer an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, allergy, asthma, or a disease caused by a pathogen.
- Such re-administration or administration may be accomplished using various modes, including catheter or injection administration or any other effective route.
- This aspect of the invention may also find use in patients who may have a limited or incomplete ability to mount an immune response or are immune compromised (e.g. patient infected with HIV and bone marrow transplant patients).
- TLR9 or TLR7 specific oligonucleotide-based compounds of the invention were added to the wells, and incubation continued for 24 h.
- cells were then stimulated with the 10 ⁇ g/ml TLR9 or TLR7 agonist for 24 h.
- the J774 cells were then treated with 0,1 1 or 3 ⁇ g/ml of TLR9 specific oligonucleotide-based compounds of the invention or control oligonucleotides and incubation continued for 48 h.
- the J774 cells were then treated with 0, or 50 ⁇ g/ml of TLR9 specific oligonucleotide-based compounds of the invention or control oligonucleotides and incubation continued for 48 h.
- cellular extracts were prepared and analyzed for the amount of TLR9 mRNA or TLR9 protein.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Oncology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Pulmonology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US27525209P | 2009-08-27 | 2009-08-27 | |
US24055309P | 2009-09-08 | 2009-09-08 | |
EP15165966.1A EP2960333B1 (fr) | 2009-08-27 | 2010-08-26 | Composition permettant d'inhiber l'expression de gènes et utilisations de celle-ci |
EP10749570.7A EP2470656B1 (fr) | 2009-08-27 | 2010-08-26 | Composition pour inhiber l'expression génique et ses utilisations |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP10749570.7A Division EP2470656B1 (fr) | 2009-08-27 | 2010-08-26 | Composition pour inhiber l'expression génique et ses utilisations |
EP15165966.1A Division EP2960333B1 (fr) | 2009-08-27 | 2010-08-26 | Composition permettant d'inhiber l'expression de gènes et utilisations de celle-ci |
Publications (1)
Publication Number | Publication Date |
---|---|
EP3272870A1 true EP3272870A1 (fr) | 2018-01-24 |
Family
ID=43446697
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP10749570.7A Active EP2470656B1 (fr) | 2009-08-27 | 2010-08-26 | Composition pour inhiber l'expression génique et ses utilisations |
EP15165966.1A Active EP2960333B1 (fr) | 2009-08-27 | 2010-08-26 | Composition permettant d'inhiber l'expression de gènes et utilisations de celle-ci |
EP17190602.7A Withdrawn EP3272870A1 (fr) | 2009-08-27 | 2010-08-26 | Compositions permettant d'inhiber l'expression de gènes et leurs utilisations |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP10749570.7A Active EP2470656B1 (fr) | 2009-08-27 | 2010-08-26 | Composition pour inhiber l'expression génique et ses utilisations |
EP15165966.1A Active EP2960333B1 (fr) | 2009-08-27 | 2010-08-26 | Composition permettant d'inhiber l'expression de gènes et utilisations de celle-ci |
Country Status (15)
Country | Link |
---|---|
US (3) | US8431544B1 (fr) |
EP (3) | EP2470656B1 (fr) |
JP (1) | JP5805088B2 (fr) |
CN (2) | CN102712926B (fr) |
CA (1) | CA2772352A1 (fr) |
DK (1) | DK2470656T3 (fr) |
ES (2) | ES2646097T3 (fr) |
HK (1) | HK1210223A1 (fr) |
HR (1) | HRP20150566T1 (fr) |
HU (1) | HUE026020T2 (fr) |
PL (1) | PL2470656T3 (fr) |
PT (1) | PT2470656E (fr) |
SI (1) | SI2470656T1 (fr) |
SM (1) | SMT201500140B (fr) |
WO (1) | WO2011031520A1 (fr) |
Families Citing this family (143)
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KR101141544B1 (ko) | 2009-03-13 | 2012-05-03 | 한국과학기술원 | 에스아이알엔에이 다중 접합체 및 이의 제조방법 |
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JP6106085B2 (ja) | 2010-08-24 | 2017-03-29 | サーナ・セラピューティクス・インコーポレイテッドSirna Therapeutics,Inc. | 内部非核酸スペーサーを含む一本鎖RNAi剤 |
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EP4141116A1 (fr) | 2011-11-18 | 2023-03-01 | Alnylam Pharmaceuticals, Inc. | Agents d'arni modifiés |
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AP2015008862A0 (en) | 2013-05-22 | 2015-11-30 | Alnylam Pharmaceuticals Inc | Tmprss6 irna compositions and methods of use thereof |
AR097738A1 (es) | 2013-09-23 | 2016-04-13 | Alnylam Pharmaceuticals Inc | Métodos para tratar o prevenir enfermedades asociadas con la transtiretina (ttr) |
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KR102592370B1 (ko) | 2014-02-11 | 2023-10-25 | 알닐람 파마슈티칼스 인코포레이티드 | 케토헥소키나제(KHK) iRNA 조성물 및 그의 사용 방법 |
TW201607559A (zh) | 2014-05-12 | 2016-03-01 | 阿尼拉製藥公司 | 治療serpinc1相關疾患之方法和組成物 |
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CN116004624A (zh) | 2015-04-03 | 2023-04-25 | 马萨诸塞大学 | 用于靶向亨廷汀mRNA的寡核苷酸化合物 |
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DE102015008536A1 (de) * | 2015-07-02 | 2017-01-05 | Rheinische Friedrich-Wilhelms-Universität Bonn | Diskontinuierliche Oligonukleotid-Liganden |
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WO2017011286A1 (fr) | 2015-07-10 | 2017-01-19 | Alnylam Pharmaceuticals, Inc. | Compositions d'arni de la sous-unité acide labile de la protéine se liant au facteur de croissance apparenté a l'insuline (igfals) et du facteur de croissance 1 apparenté a l'insuline (igf-1) et leurs procédés d'utilisation |
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- 2010-08-26 US US12/869,209 patent/US8431544B1/en active Active
- 2010-08-26 CA CA2772352A patent/CA2772352A1/fr not_active Abandoned
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- 2010-08-26 EP EP10749570.7A patent/EP2470656B1/fr active Active
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- 2010-08-26 EP EP15165966.1A patent/EP2960333B1/fr active Active
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Also Published As
Publication number | Publication date |
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US20110082186A1 (en) | 2011-04-07 |
EP2470656B1 (fr) | 2015-05-06 |
CN102712926B (zh) | 2015-04-29 |
EP2960333B1 (fr) | 2017-10-04 |
PT2470656E (pt) | 2015-07-16 |
US20120016004A1 (en) | 2012-01-19 |
HK1210223A1 (en) | 2016-04-15 |
DK2470656T3 (da) | 2015-06-22 |
CN104673795A (zh) | 2015-06-03 |
HRP20150566T1 (hr) | 2015-07-17 |
PL2470656T3 (pl) | 2015-08-31 |
ES2538347T3 (es) | 2015-06-19 |
ES2646097T3 (es) | 2017-12-12 |
SI2470656T1 (sl) | 2015-07-31 |
WO2011031520A1 (fr) | 2011-03-17 |
US8431544B1 (en) | 2013-04-30 |
HUE026020T2 (en) | 2016-05-30 |
JP5805088B2 (ja) | 2015-11-04 |
SMT201500140B (it) | 2015-09-07 |
EP2470656A1 (fr) | 2012-07-04 |
CA2772352A1 (fr) | 2011-03-17 |
EP2960333A1 (fr) | 2015-12-30 |
CN102712926A (zh) | 2012-10-03 |
JP2013507905A (ja) | 2013-03-07 |
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